SUMMARY Lung cancer?both primary and secondary as part of metastatic disease?is a significant burden on societies worldwide, and the most common cause of death in cancer patients overall. Lung resection offers a potential cure among patients with early stage disease, but leaves patients deconditioned or even disabled. Exercise intervention studies in lung cancer patients have shown benefits with respect to physical and emotional functioning. Despite this consistent evidence, to date, exercise training has not been adopted into clinical practice. We believe that for translation to the clinic to succeed, a regimen needs to be tested that can be easily integrated into the clinical flow, utilizing a limited, yet effective, scope of financial resources. In addition, exercise training will be most effective if it uses standard clinic contact points prior to surgery and post-surgery. The clinical trial that we propose here fills this gap in knowledge precisely, by testing an exercise intervention that can be readily integrated into the clinic and by obtaining data on functional efficacy and patient-reported outcomes. The trial will also examine other clinical endpoints and the cost of the intervention and patient care. The Precision Exercise Prescription (PEP) Study is a randomized controlled trial of n=177 men and women (>18 years) with primary and secondary lung cancer who are undergoing surgical treatment. Participants will be randomized either to an intervention or control group. The intervention will consist of an exercise program, tailored to the functional mobility level of the patient and supervised by a physical therapist. It begins at the pre- operative visit, continues during the inpatient period, and continues with guided home exercise and telephone counseling during the post-operative outpatient period. Our primary aim is to investigate whether the PEP intervention improves the physical function of lung cancer patients. Secondary outcomes include measurements of patient-reported outcomes, such as quality-of-life, fatigue, and self-efficacy, as well as length of stay, complication and readmission rates, pulmonary function, and treatment-related cost. PEP builds on a successful pilot study and is conducted by a highly experienced and motivated interdisciplinary team with long-standing expertise in exercise and behavioral interventions and surgery, as well as a proven track-record in bringing pre-surgery health interventions to broad implementation. The intervention is highly innovative, testing a precision exercise prescription that encompasses the pre-operative, inpatient, and post-discharge period and that can be directly translated to the clinic. We will target patients in the Salt Lake City, UT, area, as well as a large rural population that faces numerous health care challenges, to test the efficacy of our intervention in these disadvantaged populations. Our findings will have highly relevant, near- term clinical and societal impact on the implementation of exercise as a treatment modality in the care of lung cancer patients.